Use Of Pharmacological Interventions Research Articles

S225. A SYSTEMATIC REVIEW AND META-ANALYSIS OF PHARMACOLOGICAL INTERVENTIONS FOR REDUCTION OR PREVENTION OF WEIGHT GAIN IN SCHIZOPHRENIA

BackgroundWeight gain is an extremely common problem in schizophrenia patients and is associated with morbidity and mortality. We conducted a Cochrane meta-analysis to determine the effects of pharmacological interventions aimed at reduction or prevention of weight gain in schizophrenia.MethodsWe searched the Cochrane Schizophrenia Group’s Trials Register that is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There is no language, date, document type, or publication status limitations for inclusion of records in the register. We also searched reference sections within relevant papers, hand searched key journals, and contacted the first author of each relevant study and other experts to collect further information. We included all double blind randomized controlled trials examining any adjunctive pharmacological intervention for weight loss (treatment) or weight maintenance (prevention) in patients with schizophrenia or schizophrenia-like illnesses. We reliably selected, quality assessed and extracted data from studies. As endpoint and change data were combined in the analysis, mean differences (MD) of the change from baseline were calculated. The primary outcome measure was weight loss.ResultsForty-four randomized controlled trials met the inclusion criteria for this review. Ten studies examined prevention of weight gain while on antipsychotics. Reboxetine may be slightly effective in preventing weight gain (Weight: MD -2.09 kg, 95% CI -3.12 to -1.05; participants = 111; studies = 3; BMI: MD -0.70, 95% CI -1.03 to -0.36; participants = 111; studies = 3) and but the quality of evidence is low as the studies are small and have all been conducted by the same group. We are uncertain about the other agents used in a preventive role because the quality of evidence is very low.Thirty-four studies examined reduction of weight gain with pharmacological interventions. Metformin is effective in bringing about modest weight loss (MD -3.45 kg, 95% CI -4.92 to -1.98 kg; participants = 569; studies = 8; BMI: MD -1.32 kg/m2, 95% CI -1.84 to -0.81 kg/m2; participants = 606; studies = 9). This effect is probably stronger in first episode psychosis (FEP) patients (Weight: MD -5.18 kg, 95% CI -6.22 to -4.14 kg; participants = 214; studies = 3; BMI: MD -1.87 kg/m2, 95% CI -2.19 to -1.56 kg/m2; participants = 214; studies = 3) compared to chronic patients (Weight: MD -2.0 kg, 95% CI -3.0 to -1.0 kg; participants = 355; studies = 5; BMI: MD -0.73 kg/m2, 95% CI -1.04 to -0.42 kg/m2; participants = 392; studies = 6). Metformin probably decreases fasting insulin levels and insulin resistance as well. The frequency of adverse effects did not differ between metformin and placebo groups. Other agents that may reduce weight include aripiprazole, topiramate, H2 antagonists such as nizatidine, and sibutramine but the quality of the evidence is low or very low making the effects uncertain. Importantly, none of the adjunctive treatment strategies result in higher dropout rates. Other than higher reports of anxiety with aripiprazole, none of the adjunctive treatment strategies appear to result in worsening of mental status.DiscussionAccumulating evidence supports the safe use of pharmacological interventions to achieve modest weight loss. Reboxetine may be slightly effective in preventing weight gain while metformin has the most evidence for use as treatment of weight gain in schizophrenia. The small number of studies, small sample size, and short study duration limits interpretation for other agents. Future studies that are adequately powered, with longer treatment duration, will be needed in evaluating the efficacy and safety of interventions for managing weight gain further.

Anti-inflammatory therapies in myocardial infarction: failures, hopes and challenges.

In the infarcted heart, the damage-associated molecular pattern proteins released by necrotic cells trigger both myocardial and systemic inflammatory responses. Induction of chemokines and cytokines and up-regulation of endothelial adhesion molecules mediate leukocyte recruitment in the infarcted myocardium. Inflammatory cells clear the infarct of dead cells and matrix debris and activate repair by myofibroblasts and vascular cells, but may also contribute to adverse fibrotic remodelling of viable segments, accentuate cardiomyocyte apoptosis and exert arrhythmogenic actions. Excessive, prolonged and dysregulated inflammation has been implicated in the pathogenesis of complications and may be involved in the development of heart failure following infarction. Studies in animal models of myocardial infarction (MI) have suggested the effectiveness of pharmacological interventions targeting the inflammatory response. This article provides a brief overview of the cell biology of the post-infarction inflammatory response and discusses the use of pharmacological interventions targeting inflammation following infarction. Therapy with broad anti-inflammatory and immunomodulatory agents may also inhibit important repair pathways, thus exerting detrimental actions in patients with MI. Extensive experimental evidence suggests that targeting specific inflammatory signals, such as the complement cascade, chemokines, cytokines, proteases, selectins and leukocyte integrins, may hold promise. However, clinical translation has proved challenging. Targeting IL-1 may benefit patients with exaggerated post-MI inflammatory responses following infarction, not only by attenuating adverse remodelling but also by stabilizing the atherosclerotic plaque and by inhibiting arrhythmia generation. Identification of the therapeutic window for specific interventions and pathophysiological stratification of MI patients using inflammatory biomarkers and imaging strategies are critical for optimal therapeutic design.

Abstract P3-12-13: Breast atypical hyperplasia and guideline compliance

Abstract Background: Atypical hyperplasia of the breast is a high-risk benign lesion that is found in approximately 10% of benign breast biopsies[1]and confers a risk for future breast cancer[2]. The American Society of Clinical Oncology guideline states that pharmacologic risk reduction with the use of a selective estrogen receptor modulator or an aromatase inhibitor should be discussed with women with a 5-year projected absolute risk of breast cancer of 1.7% or higher[3]. The NCCN guideline for risk reduction recommends consideration of risk-reduction interventions, including the use of pharmacologic agents in women with a 5-year risk of 1.7% or higher and a life expectancy of 10 years or longer [4] .The majority of women with atypical hyperplasia meet this risk criterion with their cumulative risk of approximately 1% per year. Method: We retrospectively reviewed excisional biopsy pathology reports between January 2016 and June 2016 with the diagnosis of atypical ductal or lobular hyperplasia to identify patients with pure atypical hyperplasia. Medical records of these patients were then reviewed to identify the percentage of patients referred to a medical oncologist for chemoprevention discussion and the percentage of patients who received chemoprevention following excisional biopsy. Results: Two hundred seventy six patients with the diagnosis of atypical ductal or lobular hyperplasia were identified. Two hundred and sixteen patients were excluded from the analysis due to the presence of other histologies such as carcinoma in situ and invasive carcinoma. Medical records of the remaining sixty patients with pure atypical hyperplasia were reviewed. Eighteen patients' charts were unavailable for review. All of the remaining forty two patients had a 5-year breast cancer risk of 1.7% or higher. Five of these patients (8.3%) were referred to a medical oncologist for chemoprevention discussion. Two of these five patients (2.3%) received chemoprevention with tamoxifen. For patients who were not referred to medical oncologist, there was one documented discussion of chemoprevention with patient by her surgical oncologist. One patient underwent prophylactic bilateral mastectomies, and therefore, chemoprevention was not recommended. Conclusion: Multidisciplinary strategies need to be implemented to bridge the gap between guidelines and clinical practices which may lead to improved patient outcomes.

Impact of new diagnostic criteria for gestational diabetes.

In January 2015, the diagnostic and therapeutic criteria for gestational diabetes changed, with the goal of increasing the sensitivity of diagnosis and improving overall glycemic control, and thus reducing adverse pregnancy outcomes. Our primary aim was to evaluate the effect of the new guidelines on the incidence of diagnosis of gestational diabetes and the incidence of therapeutic interventions. Our secondary aim was to look at the incidence of adverse pregnancy outcomes. A retrospective clinical audit was conducted at a regional hospital to compare the incidence of gestational diabetes, and the specific maternal and neonatal outcomes before and after the change in guidelines was implemented. Data were collected via chart review for a 6-month period before and after the change in guidelines in January 2015. Data collected included demographics, neonatal and maternal outcomes, and the treatment type used for patients diagnosed with gestational diabetes. There was a significant increase in the incidence of diagnosis of gestational diabetes (9.8-19.6%; P < 0.001), and an overall increase in the use of pharmacological treatments for gestational diabetes. There was no significant difference in the incidence of the adverse outcomes measured, including cesarean delivery and macrosomia. There was no significant change in mean fetal weight. Despite a doubling of the incidence of diagnosis of gestational diabetes, and a consequent increase in pharmacological interventions, the change in diagnostic and therapeutic criteria did not significantly reduce the neonatal or maternal adverse outcomes measured.

Lečenje akutnog pogoršanja hronične obstruktivne bolesti pluća

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure.

What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is reported that it was also effective in reducing intubation in AECOPD with hypercapnic respiratory failure. Despite the apparent need for more supporting evidence, efforts to improve efficacy of NIV have continued unabated. It is anticipated that these efforts will, over time, serve toprogressively decrease the risk of intubation and invasive mechanical ventilation in cases of AECOPD with acute respiratory failure.

Actualización del tratamiento de la insuficiencia venosa en la gestación

Chronic venous insufficiency is a long-term pathological condition resulting from anatomical or functional alterations of the venous system. This leads to the appearance of symptoms and physical signs that affect a large part of the population and particularly pregnant women, due to the physiology of pregnancy.The few published studies on the use of pharmacological treatments of venous insufficiency in this group of the population, often makes the management of this condition difficult in routine clinical practice.A review is presented in this article, with all the latest updates in the treatment of this condition during pregnancy. There are numerous general, and some pharmacological, recommendations, that we can safely offer the pregnant patient.

Effectiveness of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Physical Injuries: A Systematic Review and Meta-Analysis of Observational Studies.

Patients with attention-deficit/hyperactivity disorder (ADHD) are more prone to physical injuries, including motor vehicle accidents, fractures and brain injuries. Several observational studies have been published investigating the association between the use of pharmacological treatment for ADHD and the incidence of physical injuries among patients with ADHD; however, the findings are not concordant. This study is a systematic review and meta-analysis of the existing literature and estimates the overall association between the use of ADHD medications and physical injury. Injury is defined as medically attended physical injuries in the form of hospitalisations, emergency department visits or general practitioners visits. The PubMed, EMBASE, PsycINFO, CINAHL and Cochrane Review databases were searched for relevant studies published up to May 2017 relating to ADHD medication and risk of injuries. Observational studies with any study design, all age groups (children and adults) and all ADHD medications (stimulant and non-stimulants) were included. Studies relevant to the association between ADHD medication exposure and risk of injuries in ADHD patients were extracted and compiled for meta-analysis. Both within-individual and between-individual analyses were conducted. Overall, 2001 citations were identified and 10 observational studies were included. Three self-controlled case series and two self-controlled cohorts were eligible for meta-analysis of within-individual studies. Five cohort studies were included in the meta-analysis of between-individual studies. The adjusted rate ratio of the within-individual methods was 0.76 (95% confidence interval [CI] 0.61-0.93) and 0.88 (95% CI 0.85-0.92) for between-individual studies. The findings of this meta-analysis support a reduced risk of injuries among ADHD patients who were treated with ADHD medications.

The implications of baseline bone-health assessment at initiation of androgen-deprivation therapy for prostate cancer.

To assess bone-density testing (BDT) use amongst prostate cancer survivors receiving androgen-deprivation therapy (ADT), and downstream implications for osteoporosis and fracture diagnoses, as well as pharmacological osteoporosis treatment in a national integrated delivery system. We identified 17 017 men with prostate cancer who received any ADT between 2005 and 2014 using the Veterans Health Administration cancer registry and administrative data. We identified claims for BDT within a 3-year period of ADT initiation. We then used multivariable regression to examine the association between BDT use and incident osteoporosis, fracture, and use of pharmacological treatment. We found that a minority of patients received BDT (n = 2 502, 15%); however, the rate of testing increased to >20% by the end of the study period. Men receiving BDT were older at diagnosis and had higher-risk prostate cancer (both P < 0.001). Osteoporosis and fracture diagnoses, use of vitamin D ± calcium, and bisphosphonates were all more common in men who received BDT. After adjustment, BDT, and to a lesser degree ≥2 years of ADT, were both independently associated with incident osteoporosis, fracture, and osteoporosis treatment. BDT is rare amongst patients with prostate cancer treated with ADT in this integrated delivery system. However, BDT was associated with substantially increased treatment of osteoporosis indicating an underappreciated burden of osteoporosis amongst prostate cancer survivors initiating ADT. Optimising BDT use and osteoporosis management in this at-risk population appears warranted.

Pharmacological treatment of patients with paraphilic disorders and risk of sexual offending: An international perspective

Objectives: The present study aims to evaluate existing policy and practice relating to the use of pharmacological treatments with patients suffering from paraphilic disorders who are at risk of committing further sexual offences.Methods: A systematic literature search was conducted to document current legal policies across 26 different countries. In addition, a questionnaire assessing the practice of pharmacological treatment was sent to practitioners involved in the treatment of patients with paraphilic disorders.Results: Legal policies concerning the preconditions of using pharmacological treatments differ considerably between countries, and for most jurisdictions do not exist. Drawing on the responses of 178 practitioners, pharmacological agents are a useful addition to psychotherapeutic interventions, especially with those patients classified as medium or high risk for sexually violent behaviours. It would appear that most patients are medically examined, are informed of the risks and possible side effects before treatment commences and are also obliged to sign a consent form.Conclusions: Although pharmacological agents can be seen as an intrusion into a patients’ sexual self determination, results indicate that ethical and clinical standards are being met in the majority of cases. However, further promotion of current WFSBP treatment guidelines would help to standardise practice across North American and European countries.

Persistent Low Rates of Treatment of Metabolic Risk Factors in People With Psychotic Disorders: A PHAMOUS Study.

People with psychotic disorders have an increased metabolic risk and a shortened life expectancy compared to the general population. Two large studies showed that metabolic disorders were untreated in a majority of the patients. Since then, guidelines have urged monitoring of metabolic health. This study examined the course of metabolic disorders over time in people with psychotic disorders and investigated current treatment rates. A total of 1,259 patients with psychotic disorders, as defined by the DSM-IV, from 4 Dutch mental health institutions participated in 3 yearly assessments of the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) between 2006 and 2014. Patients' metabolic parameters were measured, and the use of pharmacologic treatment for hypertension (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg), dyslipidemia (5% ≤ Systematic COronary Risk Evaluation [SCORE] risk < 10% and low-density lipoprotein [LDL] cholesterol level ≥ 2.5 mmol/L or SCORE risk ≥ 10% and LDL cholesterol level ≥ 1.8 mmol/L and/or triglycerides ≥ 2.3 mmol/L), and hyperglycemia (hemoglobin A1c concentration > 7% and/or fasting glucose concentration ≥ 7.2 mmol/L) was recorded. Prevalence of the metabolic syndrome, as defined by the National Cholesterol Education Program criteria, was > 50% at each assessment. On the basis of the European Society of Cardiology guidelines, pharmacotherapy for metabolic disorders was recommended for 52%-59% of the patients at each assessment. Treatment rates with antihypertensive (from 31% to 38%, P < .001) pharmacotherapy increased throughout the assessments. However, half of the patients were not treated for their metabolic risk factors while being monitored for 3 years or longer. Older patients were more likely to receive treatment, and patients who received treatment had lower blood pressure and lower cholesterol and triglyceride concentrations than patients not receiving the recommended treatment. Metabolic risk factors are still seriously undertreated in people with psychotic disorders. Better adherence to and better implementation of guidelines about monitoring and treating metabolic disorders in psychiatry are crucial.

The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.

Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I. To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults. Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates. General community. Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up. Not applicable. Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx. In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes. We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

Pain relief for outpatient hysteroscopy.

Pain relief for outpatient hysteroscopy.

Pharmacologic Interventions for Intractable and Persistent Hiccups: A Systematic Review

BackgroundChlorpromazine is the only drug approved by the US Food and Drug Administration for the treatment of hiccups; however, many other pharmacologic treatments have been proposed for intractable and persistent hiccups. Currently, there is little evidence to support the use of one agent over another. ObjectiveThis review aims to identify literature concerning the use of pharmacologic treatments for intractable and persistent hiccups with the goal of evaluating therapies in terms of their level of evidence, mechanism of action, efficacy, dosing, onset of action, and adverse effects. MethodsA systematic literature search of PubMed, Embase, the Cochrane Library, and the New York Academy of Medicine was performed to find articles where a pharmacologic agent was used to treat intractable or persistent hiccups between the years 1966 and 2016. The GRADE method was used to assess the level of evidence for the studies included in this review. ResultsThis review identified 26 articles involving 10 pharmacologic treatment options that met our inclusion criteria. Amitriptyline, baclofen, gabapentin, haloperidol, metoclopramide, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid were found in the literature to be successful in treating hiccups. ConclusionBaclofen, gabapentin, and metoclopramide were the only agents that were studied in a prospective manner, while only baclofen and metoclopramide were studied in randomized controlled trials. No specific recommendations can be made for treating intractable and persistent hiccups with the evidence currently available in the literature. Therapy selection should be specific to individual patients, their underlying comorbidities, etiology of hiccups, and take into account the individual properties of the drugs.

Development and Implementation of a Pharmacological Toolkit to Help Providers Manage Level of Consciousness Following Traumatic Brain Injury: A Quality Improvement Project

Introduction: Traumatic brain injury (TBI) is a serious public health concern in the USA. Each year, TBIs contribute to a total of 52,000 deaths, accounting for 30% of all injury-related deaths and cases of permanent disability. Approximately 5 million survivors of TBI in the USA live with some form of disability [1]. Due to the severity of the brain injuries, some patients will experience a reduced level of consciousness. Early use of pharmacological treatment is fundamental to improve patient outcomes. Background: Providers presently seek guidelines to help them choose the right medication quickly and accurately. A pharmacological toolkit was designed to help providers in the neurology unit to enhance patients’ level of consciousness and improve quality of care following a traumatic brain injury. The theoretical model for this project is the Havelock Theory of Change, which was used to guide the team during the stages of change. The Logic Model was used during the development and implementation of the toolkit. Methods: This project was developed and implemented in the medical neurological unit at the long term acute care and rehabilitation hospital. An educational program was initiated for providers to help them use the evidence based pharmacological toolkit to prescribe neuro-stimulates for patients with TBIs who demonstrated poor levels of consciousness. The Coma Recovery Scale -Revised (CRS-R) scale [2] was used to reassure if effectiveness of the neuropharmacology was feasible to treat poor alertness. The percentage of improvement on CRS-R score of 27.68%, with improvement of 3 points on CRS-R score, is a significant improvement to this QI project. The data was collected over six months and captured the variability reflecting improvement. A post implementation survey was answered by providers to track the benefit and practicability of the tool. Results: The level of satisfaction was high based on the survey response. Conclusion: Use of a neuropharmacological toolkit promises to help providers to treat severe traumatic brain injury in patients experiencing poor level of alertness. In conclusion, following the national brain injury organization recommendations, every institution needs to develop their own guideline to treat TBIs.

Evaluation of the use of pharmacological treatment with prisoners experiencing high levels of hypersexual disorder

This paper presents an evaluation of the impact of pharmacological treatment in reducing hypersexual disorder in adult males who have been incarcerated following conviction for a sexual offence. The evaluation compares two types of pharmacological treatment, one of which is part of the current NICE guidance for treatment of hypersexuality (Antiandrogens), whilst the other type (SSRIs) is off-label use in the UK for hypersexuality. The participant pool comprised 127 adult male prisoners serving sentences for sexual offences in a UK prison. Participants had been voluntarily referred for pharmacological treatment to manage hypersexual disorder. The results demonstrated a significant reduction of hypersexual disorder pre- and post-medication and contribute to the evidence base for the use of pharmacological treatment with individuals for whom hypersexual disorder may be a salient factor in their offending. Limitations of the current research are discussed.

Chronic pain in multiple sclerosis: A 10-year longitudinal study

Background and purposePain is a common symptom associated with multiple sclerosis (MS), and has lasting effects on an individual's functional capacity and quality of life. A wide range of prevalence rates of pain (between 23% and 90%)have been reported in MS and this is mainly due to the methodological differences amongst the studies such as variability in patient sources, method of sampling and the definition of pain used. Chronic pain in MS, defined as pain lasting for greater than 3–6 months, can have a significant impact on their biopsychosocial health, including negative impact on activities of daily living, relationships and social participation. The long-term course of MS-related pain and its impact in an Australian cohort over a 7-year period has been investigated earlier. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. MethodsThis was a prospective longitudinal study conducted at the Rehabilitation Department of Royal Melbourne Hospital (RMH), a tertiary referral hospital in Victoria and Australia. The source of participants was from the RMH MS database and contains detailed MS patient information including demographic data, diagnosis details (using McDonald's criteria), pain characteristics. Structured face-face interviews and validated measures were used, which include the visual analogue scale (VAS); chronic pain grade (CPG); the assessment of quality of life (AQoL) and the carer strain index (CSI). The mean age of the participants (n=70) was 55.3 years and majority (70%) were female. ResultsThe mean age of the participants (n=70) was 55.3 years and majority (70%) were female. The findings show that over time (10 years), participants report having greater bilateral bodily pain and greater description of pain as ‘worse as it could be’. Pain types were similar to 7-years follow-up but remained higher than baseline. There was a significant deterioration in quality of life in those with more severe CPG over time. Almost half of the participants 31 (44%) required care either from a private carer, institution or from a family member. Although fear of taking medications and side effects were common barriers to treatment for pain, there was an increase in the use of pharmacological treatment over time and an increase in the use of healthcare services, mainly neurologists and general practitioners. ConclusionsThe pain measures reported by the participants were similar to those at the 7-year follow-up except there was a greater representation of bilateral pain locations (limb, trunk and facial pain) compared to baseline and 7-year follow-up. At 10-year follow-up, more participants used medications compared to 7-year follow-up and there was an increase in the use of health professionals at the 10-year follow-up. At the 10-year follow up QoL of the participants deteriorated significantly and more participants had progressed to higher CPG III and CPG IV. This study demonstrates that chronic pain is a significant issue over time in MS, with clinical and health implications, impact on quality of life, disability and healthcare utilization. ImplicationsGreater awareness of chronic pain in pwMS, cognitive classifications and an interdisciplinary approach is required to improve long-term patient outcomes and well-being.

Chronic urticaria in the real-life clinical practice setting in Sweden, Norway and Denmark: baseline results from the non-interventional multicentre AWARE study.

Chronic urticaria (CU) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World-wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real-life treatment situation, burden of disease and clinical resource usage of H1-antihistamine-refractory CU patients. To examine baseline data from Scandinavian AWARE patients. AWARE is a prospective, non-interventional, multinational, umbrella design study, which includes adults (≥18 years) with a confirmed CU diagnosis (>2 months) that is refractory to H1-antihistamines. Baseline patient characteristics, disease activity (urticaria control test [UCT]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [DLQI]; chronic urticaria quality of life questionnaire [CU-Q2 oL; Danish patients only]) and work productivity and activity impairment (WPAI) scores were also assessed. Overall, 158 CU patients from seven centres in Denmark (n = 80), Norway (n = 50) and Sweden (n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m2 , respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score <12) and had a 'spontaneous' component to their CU (61.4% CSU; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non-sedative H1-antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. Adult Scandinavian H1-antihistamine-refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.

A systematic review of the effectiveness of palliative interventions to treat rectal tenesmus in cancer

Background: Rectal tenesmus is a distressing symptom in patients with advanced cancer and challenging to treat. There is lack of consensus on the appropriate management of tenesmus in this patient population. Aim: To identify and examine the effectiveness of interventions to palliate rectal tenesmus caused by advanced cancer when surgery, radiotherapy or chemotherapy are no longer treatment options. Design: A systematic review of the literature following standard systematic review methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Data sources: A comprehensive search of the electronic databases MEDLINE, EMBASE and the Cochrane Library was conducted from date of inception to April 2016. PubMed ‘related articles’ search, grey literature search and hand-searches of the bibliographies of relevant papers and textbooks were also performed. Non-cancer patients were excluded. Any studies involving surgery or radiotherapy to treat tenesmus were excluded. Studies involving interventions to treat pelvic pain syndromes without specific outcome measures on severity of tenesmus were excluded. The quality of the studies was assessed using a National Institute for Health and Clinical Excellence–recommended quality assessment tool. Results: From 861 studies, 9 met full criteria and were selected. All were case series investigating the use of pharmacological interventions (diltiazem, nifedipine, methadone, mexiletine hydrochloride, lidocaine and bupivacaine), anaesthetic interventions (lumbar sympathectomy, neurolytic superior hypogastric plexus block), and endoscopic laser interventions. The included studies showed substantial heterogeneity, and therefore, a meta-analysis was not feasible. Conclusion: From this review, we identified a significant gap in research into the palliation of rectal tenesmus. A multimodal approach may be necessary due to the complexity of the pathophysiology of tenesmus. Future research should focus on randomised controlled trials of drug therapies whose potential effectiveness is suggested by case series.

Traitements médicamenteux reçus par les enfants, adolescents et jeunes adultes avec trouble du spectre autistique en France : un état des lieux basé sur l’expérience parentale

BackgroundMedications are widely used among people with autism spectrum disorder (ASD). Few publications, however, document pharmacological prescriptions in autism in France. Our study provides an overview of the use of pharmacological treatments based on parental reports, and assesses the factors that influence their prescription. Patients and methodsWe conducted a retrospective cohort study in France from 2005 to 2007. The parents of 393 children, adolescents and adults with ASD (mean age 12.0 years (SD=8.6), range: 1–45) filled a questionnaire on their child's treatment prescription, including among others the name of the drug, the age of onset and treatment duration, and observed efficacy and side effects. ResultsOverall, 52% (n=203) of individuals have taken medication and 35% (n=139) retained the treatment, with at least two psychotropic medications in 10.5% of cases (n=40). The mean age of the first prescription was 9.4 years (SD=6.4). The mean duration of prescription was 5.0 years (SD=6.7). Atypical antipsychotics (APA) (23%, n=88) and conventional (13%, n=49) were the most commonly prescribed, followed by anticonvulsants (9%, n=36). The number of treatments received was associated with age (U=8908.5, P<0.001), severity of autism (rho=0.29; bootstrap [95% CI: 0.18–0.38]), delay in diagnosis (rho=0.13 [95% CI: 0.22–0.26]), institutionalization (U=7803.5, P<0.01) and treatment duration (rho=0.34 [95% CI: 0.21–0.52]), and was not associated with gender or socioeconomic status. A third of parents (32%, n=127) noted a global efficacy of treatment. Eleven percent (n=45) reported side effects, including sedation (6%, n=24) and weight gain (4%, n=15). The risk of adverse effects increased in case of APA (OR=56.1 [95% CI: 12.4–521.4], P<0.01), polypharmacy (U=2732.5, P<0.01) and off-label prescription (OR=2.4 [95% CI: 1.1–5.1], P=0.031). Each additional prescription increases by 2.4 times the risk of developing side effects. ConclusionThe high prevalence of people with autism who received or pursuing pharmacological treatment questions, given the poor evidence of their effectiveness and their significant side effects.